The proposal deals with the problem of reentry orthostatic intolerance that follows spaceflight. The main hypothesis is that microgravity induces a generalized reduction in the function of vascular smooth muscle and the innervating sympathetic and/or sensory nerve terminals. Also reviewed in this study are the characteristics of hindlimb unweighted (HU) rat model of microgravity. Since HU treatment has shown different effects on arterial and venous vasoconstrictor mechanisms, this suggests that HU treatment itself, and not some non-specific factors such as stress, was responsible for observed effects. Further studies will compare the effect of HU vs. control treatment in rat abdominal aorta and femoral vein and characterize mechanisms underlying the effects of HU on arterial and venous function.